Table 1.
Lactylation modification of target genes and the mechanism in diseases
| Disease type | Site of modification/enzyme | Study type | Target gene | Mechanism | References |
|---|---|---|---|---|---|
| Inflammation | Histone pan lysine lactylation | Bone marrow-derived macrophages from mice model | Arg1, Klf4 | BCAP promotes reparative macrophage transition through histone lactylation | [59] |
| Septic shock | H3K18 | The PBMC of healthy volunteers and critically ill patients | Arg1 | High H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels | [61] |
| Sepsis | Histone pan lysine lactylation/p300/CBP | RAW 264.7 cells | HMGB1 | The lactylated/acetylated HMGB1 was released from macrophages via exosome secretion which increases endothelium permeability | [32] |
| Ocular melanoma | H3K18/p300 | Tissues and ocular melanoma cells | YTHDF2 | The upregulated YTHDF2 by H3K18 lactylation and promoted oncogenesis through inhibition of TP53 and PER1 | [68] |
| Non-small cell lung cancer | H4K8 | BEAS-2B, A549, and H1299 cells | HK-1, IDH3G | Glycolytic enzymes (HK-1, PKM) and TCA cycle enzymes (SDHA, IDH3G) were, respectively, downregulated and upregulated by lactate, and increased histone lactylation in promoters of HK-1 and IDH3G | [71] |
| Tumor-infiltrating myeloid cells (TIMs) | H3K18 | Murine bone marrow-derived macrophages | METTL3 | Lactate accumulated in tumor microenvironment induced METTL3 upregulation in TIMs via H3K18 lactylation | [31] |
| Hepatocellular carcinoma (HCC) | K348/SIRT3 | HuH7 cells | CCNE2 | SIRT3 delactylated CCNE2 K348la and promoted HCC cell apoptosis and prevented HCC outgrowth in vivo | [74] |
| Hepatocellular carcinoma (HCC) |
K28 (AK2), K413 (IDH2) |
Patients’ tissues of hepatitis B virus-related HCC | AK2, IDH2 | Lactylation at K28 inhibits the function of AK2, facilitating the proliferation and metastasis of HCC cells | [75] |
| Alzheimer’s disease (AD) | H4K12 | Prefrontal cortex and hippocampus of mice and AD patients | HIF-1α, PKM, LDHA | The glycolysis/H4K12la/PKM2-positive feedback loop exacerbates microglial dysfunction in AD | [82] |
| Myocardial infarction | H3K18 | Monocyte–macrophages | LRG1, VEGFA, IL-10 | Histone lactylation facilitated transcription of LRG1, VEGFA, and IL-1, which favored a reparative environment through their anti-inflammatory and proangiogenic activities | [64] |